tbuckley/cabot-search huggingface dataset:
Immunisation status of UK-bound refugees between January, 2018, and October, 2019: a retrospective, population-based cross-sectional study
Authors: Anna Deal, Sally E Hayward, Alison F Crawshaw, Lucy P Goldsmith, Charles Hui, Warren Dalal, Fatima Wurie, Mary-Ann Bautista, May Antonnette Lebanan, Sweetmavourneen Agan, Farah Amin Hassan, Kolitha Wickramage, Ines Campos-Matos, Sally Hargreaves
Journal: The Lancet Public Health (2022)

WHO's new Immunization Agenda 2030 places a focus on ensuring migrants and other marginalised groups are offered catch-up vaccinations across the life-course. Yet, it is not known to what extent specific groups, such as refugees, are immunised according to host country schedules, and the implications for policy and practice. We aimed to assess the immunisation coverage of UK-bound refugees undergoing International Organization for Migration (IOM) health assessments through UK resettlement schemes, and calculate risk factors for under-immunisation.
The molecular and epigenetic function of the signaling molecule CD24 in germ cell tumors and its suitability as a therapeutic target using antibodies and NK-CAR cells
Authors: M.A. Skowron, D.J. Thomas, T.K. Becker, L. Kurz, S. Jostes, F. Bremmer, F. Fronhoffs, K. Funke, G.A. Wakileh, M.R. Müller, A. Burmeister, T. Lenz, A. Stefanski, K. Stühler, P. Petzsch, K. Köhrer, P. Altevogt, P. Albers, G. Kristiansen, H. Schorle, D. Nettersheim
Journal: European Urology (2022)
A phase 3, single arm, open-label study evaluating ovarian suppression following 3-month leuprolide acetate for injectable suspension in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA).
Authors: Ryan Tooker, Erika P. Hamilton, Kerlin Lynch, Stuart Atkinson, Ryan Turncliff
Journal: Journal of Clinical Oncology (2022)

TPS608 Background: In US clinical practice, GnRH agonists are widely used to suppress ovarian function in pre/perimenopausal patients with breast cancer that is moderate-to high-risk for recurrence. Despite extensive use of leuprolide acetate (LA) for ovarian suppression, regulatory approval for this indication has not been established in the US. Additionally, existing three month formulations may not reliably provide ovarian suppression, as demonstrated by escapes in estradiol (E2). An extended-release LA product with a 3-month dosing period specifically developed for ovarian suppression in patients with breast cancer could fill this unmet need. TOL2506 is a 3-month, extended-release formulation of 30 mg of LA. This combination of active drug and in situ polymeric extended release technology is expected to deliver higher exposure to drug than the currently available 3-month (22.5 mg) formulations of LA marketed for advanced prostate cancer and potentially reduce escapes in E2 over the dosing period. Methods: TOL2506A (OVELIA) is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. Approximately 250 subjects will be enrolled, with 30% aged 40 years or younger. Subjects must be premenopausal women, age 18-49, with a diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER &gt; 1% and/or, PR &gt; 1%, HER2-negative per ASCO CAP guidelines), who are candidates for ovarian suppression with endocrine therapy. For subjects receiving chemotherapy, premenopausal status will be determined, and confirmed by central lab hormone testing, prior to initiating chemotherapy. Male subjects with HR+, HER2-negative breast cancer may also be eligible, but will be evaluated for safety analyses only. Eligible subjects will enter the 48 week treatment period in 2 groups: those receiving tamoxifen concurrently with TOL2506 or those who initiate therapy with an aromatase inhibitor (AI; letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, if E2 &lt; 20 pg/mL has been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the Investigator’s discretion. Subjects will receive 4 doses of TOL2506 every 12 weeks over the 48 week study duration. Achievement of ovarian suppression will be defined as ≥ 90% of subjects with luteinizing hormone (LH) levels &lt; 4 IU/L at Week 6. Secondary endpoints include suppression of LH, E2 (&lt; 20 pg/mL for tamoxifen cohort and &lt; 2.72 pg/mL for AI cohort) and absence of menses at weeks 6, 12, 24, 36, and 48. Clinical trial information: NCT04906395.
A step forward for stress-induced ataxia
Authors: Hugo G. Marques, Pedro L. Castelhanito, Megan R. Carey
Journal: Trends in Neurosciences (2022)

Patients with episodic ataxia type 2 (EA2) display attacks of severe incoordination and dystonia that can be triggered by stress. In a recent study, Snell, Vitenzon, Tara, and colleagues found a mechanistic pathway by which norepinephrine (NE) alters cerebellar Purkinje output to trigger attacks in a mouse model of EA2 and identified a pharmacological intervention that effectively reduces them.
Thulium fibre laser achieves faster lithotripsy during ureteroscopic treatment of upper urinary tract stones: An observational study emulating a target trial
Authors: E. Ventimiglia, M. Corrales Acosta, M. De Angelis, P. Dioni, C. Corsini, M. Fantin, L. Candela, A. Briganti, F. Montorsi, L. Villa, A. Salonia, O. Traxer
Journal: European Urology (2022)
Impacts of hepatitis b infection in patients with head and neck squamous carcinoma.
Authors: Cheng-Lun Lai, Yu-Chen Su, Cheng-Hsien Lin, Cheng-wei Chou
Journal: Journal of Clinical Oncology (2022)

e18051 Background: Hepatitis B Virus (HBV) infection was known to be have impacts of occurrence and survival in different malignancies. We aim to evaluate the clinical association with head and neck squamous cell cancer (HNSCC) and HBV infection. Methods: A retrospective review was conducted on the medical records and cancer registry database at the Taichung Veterans General Hospital (Taichung, Taiwan) between January 2007 and December 2015. Patients with histologically proven squamous cell carcinoma of oral cavity, oropharynx, hypopharynx and larynx were enrolled in the study. HBV infection was defined as HBsAg seropositivity. Clinical features, hepatic function test and five-year overall survival (OS) were compared between patients with and without HBV infection. Results: A total of 1826 HNSCC patients were analyzed. 225 of them (12.3%) were proved HBV-infected. The HBV-infected patients was diagnosed at younger age (&lt; 65 years; 76.1% vs. 65.5%, p&lt; 0.012) and had a higher proportion of initial liver cirrhosis (11.6% vs. 3.6%, p&lt; 0.001) and hepatic dysfunction (10.7% vs. 6.1%, p= 0.009) included elevation of alanine transaminase (ALT), aspartate transaminase (AST) and prothrombin time expressed as international normalized ratio (INR). The other baseline characteristics were similar. The five-year OS were 52.9% and 48.6% in the HNSCC patients with or without HBV infection, respectively ( p= 0.341). The incidence of later founded hepatic dysfunction during follow-up was similar (31.1% vs 26.2%, p= 0.122). Conclusions: Information from this study indicated that HBV-infected HNSCC patients may present in younger age, more initial liver cirrhosis, and hepatic dysfunction. However, HBV infection did not have negative impacts on survival outcome and later founded hepatic dysfunction in those patients. Characteristics and survival of HBsAg (+) vs. HBsAg (-) HNSCC Patients[Table: see text]
Comparison of PET-based criteria of evaluation of response to immunotherapy in patients with advanced melanoma.
Authors: Francesca Comito, Rachele Pagani, Marta Aprile, Valentino Dragonetti, Norma Bonazzi, Giacomo Battisti, Claudio Malizia, Cristina Nanni
Journal: Journal of Clinical Oncology (2022)

e21536 Background: Immune checkpoint inhibitors (ICI), such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1), have evolved as a dominant strategy in the treatment of metastatic melanoma (MM) in the last decade. At least three PET-based criteria are available for the early assessment of response to immunotherapy: PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and European Organization for Research and Treatment of Cancer (EORTC) criteria. The aim of this study was evaluation of the concordance of different PET-based criteria for the assessment of response to immunotherapy and to assess their capability of properly stratifying patients in terms of overall survival (OS) and progression free survival (PFS). Methods: We retrospectively enrolled patients with the following inclusion criteria: diagnosis of MM, treatment with ICI for MM and tumor assessment performed by at least two [18F]F-fluorodeoxyglucose (FDG) PET/CT scans (a baseline and ad interim scan). [18F]F-FDG PET/CT scans were analyzed according to PECRIT, PERCIMT and EORTC criteria. Agreement was assessed using Fleiss' kappa and Cohen’s kappa. Prognostic curves of PET/CT response according to different criteria were evaluated in terms of PFS and OS by Kaplan-Meier estimates and were compared by log-rank test. Results: From December 2021 to January 2022, 30 patients were enrolled. 18/30 patients received nivolumab, 8/30 pembrolizumab, 3/30 ipilimumab and 1/30 the combination of nivolumab and ipilimumab. According to PECRIT criteria, 6 patients achieved complete metabolic response (CMR), 7 partial metabolic response (PMR), 5 stable metabolic disease (SMD) and 12 (40%) progressive metabolic disease (PMD). By PERCIMT criteria, 6 patients had response classified as CMR, 9 PMR, 8 SMD and 7 (23.4%) PMD. Finally, by EORTC criteria there were 6 CMR, 10 PMR, 2 SMD and 12 (40%) PMD. In 9 cases out of 30, one criteria assessment differed from the other two and in one patient each criteria evaluation differed from the others (PMD by PECRIT, SMD by PERCIMT, PMR by EORTC). The percentage of patients concordantly evaluated by the three criteria was 68% (Fleiss’ kappa = 0.68). PECRIT and EORTC criteria showed the highest agreement (Cohen’s kappa 0.719), followed by PERCIMT and PERCRIT (Cohen’s kappa 0.69). PERCIMT and EORTC showed 64.4% of concordance. Furthermore, all three criteria were successful in stratifying patients in terms of OS and PFS (p-value &lt; 0.05). Conclusions: We observed substantial agreement among different PET evaluation criteria, with PECRIT and EORTC criteria showing the highest concordance. Analysis of a larger population is needed to prove the utility of PET response evaluation in early prognostic stratification.
DIPG-51. Hydrocephalus Treatment and the Effect on Survival in Diffuse Intrinsic Pontine Glioma
Authors: Joshua Baugh, Nada Ben Mohammed, Sophie Veldhuijzen van Zanten, Christof Kramm, Veronica Biassoni, Maura Massimino, Dannis van Vuurden
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Diffuse intrinsic pontine glioma (DIPG), can cause hydrocephalus and if symptomatic, leads to rapid changes in consciousness requiring surgical intervention. The effect of cerebrospinal fluid (CSF) diversion on overall survival and the clinical factors influencing outcome remain unclear. The aim of this study was to evaluate the impact of the treatment of hydrocephalus on survival in DIPG patients. METHODS: The study was retrospective in design using data from the SIOPE-European Society of Pediatric Oncology DIPG Registry. Hydrocephalus was determined based on a centrally reviewed diagnostic MRI. The Kaplan-Meier method was used for survival statistics. Clinical prognostic factors including: duration of symptoms, age and cranial nerve palsy at diagnosis were evaluated for confounding and effect modification. The effect of hydrocephalus treatment (CSF diversion) on survival was examined using Cox regression. RESULTS: Among 582 patients from the SIOPE-DIPG Registry, 86 (14%) had hydrocephalus at diagnosis. Median OS for hydrocephalus patients treated with CSF diversion (n=43) was 13 months (95% CI, 10.2-17.7) and 9 months (95% CI, 7.4-10.6) for hydrocephalus patients without a CSF diversion (n=43). Survival rates were not significantly different (p=.41). On adjusted Cox regression, correcting for duration of symptoms, hydrocephalus patients with signs of cranial nerve palsy at diagnosis and a CSF diversion had a hazard ratio 0.476 (p=0.004). CONCLUSION: Survival among DIPG patients presenting with hydrocephalus at diagnosis was not influenced by CSF diversion. Hydrocephalus patients with signs of cranial nerve palsy at diagnosis, had a significantly reduced risk after undergoing CSF diversion. There is an indication this subgroup of DIPG patients may benefit more from CSF diversion, although the relationship between hydrocephalus and cranial nerve palsy requires further investigation.
The impact of virtual oncology care on chemotherapy continuity and clinical outcomes in patients treated for colorectal cancer: A pre-post analysis of the COVID-19 pandemic.
Authors: William James Phillips, Macyn Leung, Kednapa Thavorn, Timothy R. Asmis
Journal: Journal of Clinical Oncology (2022)

e13649 Background: The coronavirus (COVID-19) pandemic has resulted in an abrupt transition to virtual oncology care at most cancer centres worldwide. A pillar of the American Medical Association’s proposed framework for digitally enabled care is assessing clinical quality, safety, and outcomes. This study’s objective is to evaluate chemotherapy quality and clinical outcomes in patients receiving intravenous chemotherapy for colorectal cancer before and during the COVID-19 pandemic. Methods: This is an observational study assessing patients treated with intravenous chemotherapy for colorectal cancer consecutively at the Ottawa Hospital Cancer Centre from June 2019 to September 2021. Patients with non-metastatic rectal cancer were excluded. Patient were stratified by whether they were started on chemotherapy pre-pandemic (June 2019 – Jan 2020) versus intra-pandemic (Feb 2020 – Sept 2021). Baseline characteristics and treatment data were collected from the electronic medical records. Outcomes of interest included chemotherapy delays, dose reductions, emergency department (ED) visits and hospitalizations. We used generalized linear and binary logistic regression modelling to compare outcomes between pre- and intra-pandemic periods. Results: There were 220 patients included in this study with 108 (49%) diagnosed with metastatic disease. In total, there were 66 (30%) patients treated in the pre-pandemic and 154 (70%) in the intra-pandemic period. As expected, virtual care consultations increased during the pandemic from 1.5% to 43.5% (p &lt; 0.001). Likewise, the proportion of follow-up visits also increased from 37% to 84% (p &lt; 0.001). There was no difference in the incidence of treatment delays (odds ratio [OR] = 1.01, p = 0.78), dose reductions (OR = 0.99, p = 0.69), ED visits (OR = 1.23, p = 0.37), hospitalizations (OR = 0.73, p = 0.43) or the total length of time off treatment (OR = 0.85, p = 0.17) between the pre- and intra-pandemic periods by multivariable analysis. A subgroup analysis was performed based on stage, which showed no difference in outcomes independent of the presence of metastases. Conclusions: This study demonstrates no significant difference in chemotherapy interruptions, dose intensity, or clinical outcomes in patients treated for colorectal cancer during the COVID-19 pandemic. These findings serve as an important quality-care indictor and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients. Future work dedicated to other tumor sites would allow for broader application of these findings.
EPEN-07. Brain-tumor communication reveals potential new therapeutic targets for pediatric ependymoma
Authors: Roberta Antonelli, Carlos Jiménez, Tiziana Servidei, Riccardo Riccardi, Elena Martínez-Saez, Josep Sánchez de Toledo, Josep Roma, Soledad Gallego, Anna Llort, Lucas Moreno, Miguel Segura
Journal: Neuro-Oncology (2022)

Abstract Pediatric brain tumors (PBTs) represent the most common solid malignancies in children and the leading cause of cancer-related deaths. Despite the fact that survival after a high-grade brain tumor diagnosis is slowly improving, overall survival remains poor compared with most other cancers, thereby highlighting the need for new therapies. This is particularly true for Ependymoma (EPN), the second most common PBT that, despite advances in the understanding of EPN biology, still shows a poor prognosis in approximately 40% of patients. Accumulative evidence reveals that the transcriptome of tumors can be modulated by the host tissue, with brain tumors or brain metastasis derived from extracranial tumors being at the forefront of these studies. Our hypothesis is that understanding the impact of brain-tumor communication may open up new opportunities for therapeutic intervention. To characterize gene expression changes in Ependymoma tumors caused by the tumor microenvironment the transcriptome of patient-derived EPN cells was analyzed comparing in vitro cultured cells, subcutaneous xenografts and orthotopic xenografts. 2734 differentially expressed genes were found after comparing in vitro grown cells versus brain xenografts. Sixty-five of those genes were also differentially expressed when comparing human expression data from aggressive EPN versus the rest of EPN tumours. Among these candidates NTRK2 and CALB2 stand out. Gene depletion phenotype using multiple shRNA showed that the in vivo tumor growth of NTRK2-depleted cells, (but not CALB2) was remarkably reduced compared with control cells. These results suggest that NTRK2 could be a potential new therapeutic target for the treatment of Ependymoma
A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis
Authors: Mengna Li, Jing-Wei Xu, Jiayong Li, Wei Wang, Chenqi Luo, Haijie Han, Zhi-Kang Xu, Ke Yao
Journal: Bioactive Materials (2022)

Postoperative endophthalmitis (POE) has been the most threatening complication after cataract surgery, which perhaps can be solved by the antibiotic-loaded intraocular lens (IOL). However, most drug-loaded IOLs demonstrate insufficient drug quantity, short release time, increased implantation-related difficulties or other noticeable drawbacks. To prevent POE and to address these deficiencies, a drug-loaded copolymer IOL, prepared from poly (urethane acrylate) prepolymer, isobornyl methacrylate (IBOMA), N-vinyl-2-pyrrolidone (NVP), Irgacure 819, RUVA-93, and gatifloxacin (GAT), was rapidly fabricated via photocuring and by using a 3D-printed mold. This composite displayed an outstanding and controllable GAT release behavior in vitro, a high light transmittance, and a moderate refractive index. Also, it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material. In vivo tests demonstrated satisfying released drug concentration at the early treatment stage. In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL, which also displayed good biocompatibility. These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE, also the proposed methods could inspire more designs for various medical applications.
Variation of use of targeted therapies and molecular diagnostic testing by practice type for non-small cell lung cancer and colorectal cancer.
Authors: Thomas Roberts, Kenneth L. Kehl, Gabriel A. Brooks, Lynette M. Sholl, Alexi A. Wright, Barbara Bai, Mary Beth Landrum, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2022)

6551 Background: Targeted therapies are important first-line treatments for many patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). All patients with newly-diagnosed metastatic NSCLC and CRC should undergo molecular diagnostic testing to guide treatment selection. Methods: We used 100% Medicare fee-for-service data from 2015 through 2019 to identify beneficiaries with incident metastatic NSCLC or CRC receiving systemic therapy and to assign beneficiaries to oncology practices. We then assessed for use of molecular diagnostic testing and targeted therapies in these cohorts. We used linear mixed effects models to assess patient and practice characteristics associated with molecular diagnostic testing and targeted therapy use. Results: Rates of molecular diagnostic testing increased between 2015 and 2019 for NSCLC and CRC. In 2019, rates of molecular diagnostic testing were 85% and 65% for NSCLC and CRC, respectively. Rates of targeted therapy use did not increase over time for NSCLC or CRC, and were 8% and 5%, respectively, in 2019. Compared to National Cancer Institute (NCI)-designated cancer centers, rates of molecular diagnostic testing for CRC were 3.7 percentage points lower at practices associated with non-academic hospitals and 10.6 percentage points lower at small independent practices. Rates of targeted therapy use for NSCLC were 4.8, 5.9 and 5.5 percentage points lower at academic medical centers, large independent practices and small independent practices, respectively, compared to NCI centers. Conclusions: Rates of molecular diagnostic testing for NSCLC and CRC increased in recent years, but testing rates remain below recommended levels, and targeted therapy use remains low. Substantial variation in testing and targeted therapy use by practice type suggest that the practice where a patient is treated may impact access to recommended testing and efficacious treatments. [Table: see text]